T-lymphocyte functions in acute leukaemia patients with severe chemotherapy-induced cytopenia: characterization of clonogenic T-cell proliferation.
Intensive chemotherapy for acute leukaemia is followed by a period of severe chemotherapy-induced leukopenia. We used a limiting dilution assay to investigate whether remaining CD4+ and CD8+ T lymphocytes derived from such leukopenic patients could be activated and undergo clonogenic proliferation. The activation signal in our model was accessory cells (irradiated normal peripheral blood mononuclear cells) + phytohaemagglutinin (PHA) + interleukin-2 (IL-2). During severe leukopenia a majority of circulating lymphocytes were CD4+ T cells. Clonogenic proliferating T lymphocytes were detected for all patients. Higher frequencies of clonogenic cells were detected in the CD8+ subset as compared to the CD4+ subset. However, for both subsets frequencies of proliferating cells were decreased compared with healthy individuals. The CD4+ and CD8+ lymphocytes were also capable of proliferation in response to alloactivation, and accessory cells mainly containing acute myelogenous leukaemia blast were efficient as accessory cells for activation. For the CD4+ cells, increased proliferation was detected in the presence of acute myelogenous leukaemia (AML) blasts compared with normal accessory cells. Based on our results we conclude that: (1) although acute leukaemia patients with therapy-induced leukopenia have both a quantitative and a qualitative T-cell defect, (2) the remaining T-cell population includes a subset capable of clonogenic proliferation. However, (3) proliferation of the clonogenic CD4+ cells can be modulated by AML blasts.
Bruserud
O
O
Section for Haematology, Gade Institute, Haukeland Hospital, University of Bergen, Norway.
Ulvestad
E
E
Berentsen
S
S
Bergheim
J
J
Nesthus
I
I
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D016516:CD4-CD8 Ratio; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000097:blood* / Q000188:drug therapy; D007970:Leukopenia / Q000097:blood / Q000139:chemically induced / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood* / Q000188:drug therapy; D013601:T-Lymphocytes / Q000276:immunology*